Extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a tumor cell surface molecule that is known to promote tumor growth in epithelial malignancies and is highly expressed in head and neck squamous cell carcinoma (HNSCC). We hypothesize that CD147 can be exploited as a therapeutic target in head and neck cancer. We propose to assess the potential of anti-CD147 antibody therapy alone and in combination with concurrent radiation and cisplatin treatment. Furthermore, we propose to determine the role of CD147 in promoting regional metastasis. Although CD147 is known to stimulate fibroblasts to produce matrix metalloproteases (MMPs) and vascular endothelial growth factor (VEGF), we have identified upregulation and secretion of interleukin-12 (IL- 12) in CD147 stimulated fibroblasts. We propose to determine if CD147 promotes the malignant phenotype in vitro and in vivo tumor through modulation of IL-12. PUBLIC HEALTH RELEVANCE: Survival rates for head and neck cancer (HNSCC) have not significantly improved over the past 30 years despite more aggressive treatment and advances in medical treatment. Development of targeted agents against molecules that promote tumor growth have the potential to improve patient outcomes when combined with conventional cytotoxic therapies. We propose to determine if extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a potential molecular target in HNSCC. The application also seeks to identify the role of CD147 in tumor growth and metastasis using murine orthotopic models of head and neck cancer. Furthermore, novel molecular mechanisms by which CD147 acts to promote the malignant phenotype in vitro and in vivo will be investigated.